Modeling Nanomechanical Strains in Healthy and Diseased Single-Cells Due to Applied Fluidic Stresses

Author(s):  
Zachary D. Wilson ◽  
Sean S. Kohles

Advancements in technologies for assessing biomechanics at the cellular level have led to discoveries in the relationship between mechanics and biology (mechanotransduction) and the investigation of cell mechanics as a biomarker for disease [1]. With the recent development of an integrated optical tweezer with micron resolution particle image velocimetry (436 nm spatial resolution), the opportunity to apply controlled multiaxial stresses to suspended single cells is available [2]. A stress analysis was applied to experimental and theoretical flow velocity gradients of suspended cell-sized polystyrene microspheres in microfluidic environments representing the relevant geometry of non-adhered spherical cells as observed for osteoblasts, chondrocytes, and fibroblasts [3]. That analysis identified a very low level of applied stresses available during creeping laminar flow within straight and cross-junction microfluidic channel arrangements with uniform and extensional flows, respectively. As a followup study, the objective here was to apply a range of normal and shear stress profiles in a two-dimensional, computational analysis and estimate the responding cellular strains.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Soo-Yeon Cho ◽  
Xun Gong ◽  
Volodymyr B. Koman ◽  
Matthias Kuehne ◽  
Sun Jin Moon ◽  
...  

AbstractNanosensors have proven to be powerful tools to monitor single cells, achieving spatiotemporal precision even at molecular level. However, there has not been way of extending this approach to statistically relevant numbers of living cells. Herein, we design and fabricate nanosensor array in microfluidics that addresses this limitation, creating a Nanosensor Chemical Cytometry (NCC). nIR fluorescent carbon nanotube array is integrated along microfluidic channel through which flowing cells is guided. We can utilize the flowing cell itself as highly informative Gaussian lenses projecting nIR profiles and extract rich information. This unique biophotonic waveguide allows for quantified cross-correlation of biomolecular information with various physical properties and creates label-free chemical cytometer for cellular heterogeneity measurement. As an example, the NCC can profile the immune heterogeneities of human monocyte populations at attomolar sensitivity in completely non-destructive and real-time manner with rate of ~600 cells/hr, highest range demonstrated to date for state-of-the-art chemical cytometry.


2021 ◽  
Vol 125 (4) ◽  
pp. 1269-1278
Author(s):  
Lisa M. Dempsey ◽  
Justin J. Kavanagh

The relationship between motor function and cholinergic circuitry in the central nervous system is complex. Although many studies have approached this issue at the cellular level, few studies have examined cholinergic mechanisms in humans performing muscle contractions. This study demonstrates that blockade of muscarinic acetylcholine receptors enhances motor evoked potentials (elicited with transcranial magnetic stimulation) following strong muscle contractions, but not weak muscle contractions.


Lab on a Chip ◽  
2020 ◽  
Vol 20 (3) ◽  
pp. 601-613 ◽  
Author(s):  
Zhanshi Yao ◽  
Ching Chi Kwan ◽  
Andrew W. Poon

An optofluidic cell stretcher using a periodically chopped optical tweezer and a microfluidic flow for non-contact, continuous cell mechanical characterization.


2006 ◽  
Vol 290 (3) ◽  
pp. C672-C677 ◽  
Author(s):  
Maja Potokar ◽  
Marko Kreft ◽  
Helena H. Chowdhury ◽  
Nina Vardjan ◽  
Robert Zorec

A key step in the intrinsic apoptotic pathway is the assembly of the apoptosome complex. The apoptosome components are well known; however, the physiology of the assembly of the apoptosome complex at the cellular level is still poorly defined. The aim of this work was to study the subcellular distribution of the apoptosome scaffold protein apoptotic protease-activating factor 1 (Apaf-1) before and after triggering apoptosis in single somatotrophs. Somatotrophs are the subject of extensive pituitary tissue remodeling in different physiological situations in which the quality and the number of pituitary cells are determined by cell proliferation and apoptosis. We show herein that 2 h after triggering apoptosis with rotenone, Apaf-1 redistributed to the proximity of mitochondria. In addition, the degree of colocalization between Apaf-1 and fluorescently labeled caspase-9 significantly increased during the same period. Furthermore, we show herein for the first time in single cells that the colocalization between Apaf-1 and cytochrome c increases only transiently, indicating a transient interaction between cytochrome c and Apaf-1 during the activation of apoptosis in these cells.


2019 ◽  
Vol 57 (10) ◽  
pp. 1546-1555 ◽  
Author(s):  
Etienne Cavalier ◽  
Richard Eastell ◽  
Niklas Rye Jørgensen ◽  
Konstantinos Makris ◽  
Symeon Tournis ◽  
...  

Abstract Background Biochemical bone turnover markers (BTM) are useful tools to assess bone remodeling at the cellular level. N-terminal propeptide of type I procollagen (PINP) has been recommended as a reference marker for bone formation in research studies. Methods We describe the results of a multicenter study for routine clinical laboratory assays for PINP in serum and plasma. Four centers (Athens, Greece [GR], Copenhagen, Denmark [DK], Liege, Belgium [BE] and Sheffield, United Kingdom [UK]) collected serum and plasma (EDTA) samples from 796 patients presenting to osteoporosis clinics. Specimens were analyzed in duplicate with each of the available routine clinical laboratory methods according to the manufacturers’ instructions. Passing-Bablok regressions, Bland-Altman plots, V-shape evaluation method and the concordance correlation coefficient for PINP values between serum and plasma specimens and between methods were used to determine the agreement between results. A generalized linear model was employed to identify possible variables that affected the relationship between the methods. Results We showed that both EDTA plasma and serum were suitable for PINP determination. We observed a significant proportional bias between Orion radioimmunoassay and the automated methods for PINP (Roche Cobas and IDS iSYS), which both gave very similar results. The multivariate model did not improve the excellent correlation that was observed between the methods. Conclusions Harmonization of PINP assays is possible by applying a correction factor or correctly assigning the values of the calibrators. This work will benefit from further collaboration between assays manufacturers and clinical laboratory professionals.


Author(s):  
Stuart J. Williams ◽  
Steven T. Wereley

Understanding the fluid dynamics around a particle in suspension is important for a complete investigation of many hydrodynamic phenomena, including microfluidic models. A novel tool that has been used to analyze fluid velocity fields in microfluidics is micro-resolution particle image velocimetry (μPIV) [1]. Dielectrophoresis (DEP) is a technique that can translate and trap particles by induced polarization in the presence of nonuniform electric fields. In this paper, DEP has been used to capture and suspend a single 10.1μm diameter spherical particle in a microfluidic channel. μPIV is then used with smaller tracer particles (0.5μm) to investigate the hydrodynamics of fluid flow past the trapped particle.


Complexity ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Wenzheng Bao ◽  
Bin Yang ◽  
Rong Bao ◽  
Yuehui Chen

Lysine lipoylation is a special type of posttranslational modification in both prokaryotes’ and eukaryotes’ proteomics researches. Such a modification takes part in several significant biological processions and plays a key role in the cellular level. In order to construct and design an accurate classification algorithm for identifying lipoylation sites in the protein level, the computational approaches should be taken into account in this field. Meanwhile, several factors plays different role in the identification of modification sites. Considering such a situation, the foundational elements of the effective identification of modification sites are the available feature description and the high effective classification. With these two elements, the distinguishing between the lipoylation samples and the nonlipoylation samples can be treated as a typical classification issue in the field of machine learning. In this work, we have proposed a method named LipoFNT, which employed the two featuring sets, including the Position-Specific Scoring Matrix and bi-profile Bayesian, as the classification features. And then, the flexible neural tree algorithm is utilized to deal with the imbalance classification issue in lipoylation modification sample dataset. The proposed method can achieve 81.07% in sn%, 80.29% in sp, 80.68% in Acc, 0.8076 in F1, and 0.6136 in MCC, respectively. Meanwhile, we have demonstrated the relationship between the lengths of peptide and identification of modification sites.


2020 ◽  
Vol 19 (5-6) ◽  
pp. 343-349
Author(s):  
Sara S Fonseca Costa ◽  
Marc Robinson-Rechavi ◽  
Jürgen A Ripperger

Abstract Aging and circadian rhythms are two biological processes that affect an organism, although at different time scales. Nevertheless, due to the overlap of their actions, it was speculated that both interfere or interact with each other. However, to address this question, a much deeper insight into these processes is necessary, especially at the cellular level. New methods such as single-cell RNA-sequencing (scRNA-Seq) have the potential to close this gap in our knowledge. In this review, we analyze applications of scRNA-Seq from the aging and circadian rhythm fields and highlight new findings emerging from the analysis of single cells, especially in humans or rodents. Furthermore, we judge the potential of scRNA-Seq to identify common traits of both processes. Overall, this method offers several advantages over more traditional methods analyzing gene expression and will become an important tool to unravel the link between these biological processes.


1978 ◽  
Vol 77 (2) ◽  
pp. 377-388 ◽  
Author(s):  
PF Bartlett ◽  
M Edidin

The rate of collection of embryo fibroblast single cells by an embryo fibroblast monlayer was realted to the H-2 haplotype of the fibroblast monolayer. The rate was highest for the H-2s strains and lowest for the H-2k strains with all other strains examined being intermediate. As opposed to monolayers prepared from the A and C3H background animals, monolayers from B10 background mice only demonstrated an H-2 haplotype dependent rate differential after treatment with fetal calf serum or neuraminidase. The relationship that was seen between monolayer H-2 haplotype and rate of adhesion with embryonic monolayers was not observed with either congenic 3T3 cell lines or fibroblasts derived from adult tissues. It was further shown that the rate of single cell pick-up could be substantially reduced by incubating the monolayers with the appropriate polyspecific anti-H-2 antisera. The inhibition observed appeared to be directly related to anti-H-2 antibody binding and was not merely a function of ligand binding to the cell surface, as antisera directed against other fibroblast cell surface antigens did not significantly inhibit the adhesive rate. These results indicate a role for the H-2 gene complex in modulating fibroblast-fibroblast intercellular adhesion.


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